The program's objectives are to: 1) isolate and characterize potential ectopic growth factors which resemble epidermal growth factor (EGF) or multiplication-stimulating activity (MSA) in normal and tumor tissues of rat mammary epithelium (RME) both in vivo from tumor interstitial fluid (TIF) and in vitro from conditioned medium of primary cultures of tumor and RME cells; 2) to determine their biological, biochemical and antigenic similarities to native EGF or MSA; 3) to compare their effects on the growth and/or differentiation of mouse embryonal carcinoma cells (EC), normal rat mammary epithelial cells and human diploid fibroblasts and 4) to delineate their relationship in normal, preneoplastic and neoplastic tissues to tumor promotion and progression.